{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:19:19Z","timestamp":1791145159894,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL118408"],"award-info":[{"award-number":["HL118408"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI128527"],"award-info":[{"award-number":["AI128527"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Postinfluenza bacterial pneumonia is a significant cause of hospitalization and death in humans. The mechanisms underlying this viral and bacterial synergy remain incompletely understood. Recent evidence indicates that influenza-induced IFNs, particularly type I IFN (IFN-I) and IFN-\u03b3, suppress antibacterial defenses. In this study, we have investigated the relative importance and interplay of IFN-I and IFN-\u03b3 pathways in influenza-induced susceptibility to Streptococcus pneumoniae infection. Using gene-deficient mouse models, as well as in vivo blocking Abs, we show that both IFN-I and IFN-\u03b3 signaling pathways contribute to the initial suppression of antibacterial immunity; however, IFN-\u03b3 plays a dominant role in the disease deterioration, in association with increased TNF-\u03b1 production and alveolar macrophage (AM) depletion. We have previously shown that IFN-\u03b3 impairs AM antibacterial function and thereby acute bacterial clearance. The findings in this study indicate that IFN-\u03b3 signaling also impairs AM viability and \u03b1\u03b2 T cell recruitment during the progression of influenza\/S. pneumoniae coinfection. Macrophages insensitive to IFN-\u03b3 mice express a dominant-negative mutant IFN-\u03b3R in mononuclear phagocytes. Interestingly, macrophages insensitive to IFN-\u03b3 mice exhibited significantly improved recovery and survival from coinfection, despite delayed bacterial clearance. Importantly, we demonstrate that IFN-I receptor signaling is essential for preventing IFN-\u03b3 hyperproduction and animal death during the progression of postinfluenza pneumococcal pneumonia.<\/jats:p>","DOI":"10.4049\/jimmunol.2101135","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T19:13:32Z","timestamp":1657739612000},"page":"128-135","source":"Crossref","is-referenced-by-count":15,"title":["Type I IFN Signaling Is Essential for Preventing IFN-\u03b3 Hyperproduction and Subsequent Deterioration of Antibacterial Immunity during Postinfluenza Pneumococcal Infection"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3990-0343","authenticated-orcid":false,"given":"Sunil","family":"Palani","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Bansal","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul K","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-9582","authenticated-orcid":false,"given":"Christopher","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjun","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0045-9669","authenticated-orcid":false,"given":"Md Bashir","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keer","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"},{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,1]]},"reference":[{"key":"2025021008183058100_r1","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.4049\/jimmunol.1301152","article-title":"Immune dysfunction and bacterial coinfections following influenza","volume":"191","author":"Metzger","year":"2013","journal-title":"J. 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